Comparative pharmacokinetics and bioavailability of four alkaloids in different formulations from Corydalis decumbens

Wu, Chunyan; Yan, Ran; Zhang, Rongjin; Bai, Fan; Yang, Ye; Wu, Zhaoyang; Wu, Anming

doi:10.1016/j.jep.2013.05.043

Cited by 24 publications

(12 citation statements)

References 19 publications

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“…Numerous acetyltransferase, carboxylesterase, and CYP82 candidates with possible involvement in phthalideisoquinoline biosynthesis were identified in H. canadensis and C. chelanthifolia transcriptomes. Corydalis species accumulate the hemiacetal egenine [ 52 ], which may require a noscapine synthase (NOS)-like enzyme for hypothesized conversion to bicuculline [ 12 ]. Six candidates were identified in C. chelanthifolia with up to 52 % identity to P. somniferum NOS, although expression was very low in some cases (Additional file 7 ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants

et al. 2015

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BackgroundBenzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites sharing a common biosynthetic origin beginning with tyrosine. Many BIAs have potent pharmacological activities, and plants accumulating them boast long histories of use in traditional medicine and cultural practices. The decades-long focus on a select number of plant species as model systems has allowed near or full elucidation of major BIA pathways, including those of morphine, sanguinarine and berberine. However, this focus has created a dearth of knowledge surrounding non-model species, which also are known to accumulate a wide-range of BIAs but whose biosynthesis is thus far entirely unexplored. Further, these non-model species represent a rich source of catalyst diversity valuable to plant biochemists and emerging synthetic biology efforts.ResultsIn order to access the genetic diversity of non-model plants accumulating BIAs, we selected 20 species representing 4 families within the Ranunculales. RNA extracted from each species was processed for analysis by both 1) Roche GS-FLX Titanium and 2) Illumina GA/HiSeq platforms, generating a total of 40 deep-sequencing transcriptome libraries. De novo assembly, annotation and subsequent full-length coding sequence (CDS) predictions indicated greater success for most species using the Illumina-based platform. Assembled data for each transcriptome were deposited into an established web-based BLAST portal (www.phytometasyn.ca) to allow public access. Homology-based mining of libraries using BIA-biosynthetic enzymes as queries yielded ~850 gene candidates potentially involved in alkaloid biosynthesis. Expression analysis of these candidates was performed using inter-library FPKM normalization methods. These expression data provide a basis for the rational selection of gene candidates, and suggest possible metabolic bottlenecks within BIA metabolism. Phylogenetic analysis was performed for each of 15 different enzyme/protein groupings, highlighting many novel genes with potential involvement in the formation of one or more alkaloid types, including morphinan, aporphine, and phthalideisoquinoline alkaloids. Transcriptome resources were used to design and execute a case study of candidate N-methyltransferases (NMTs) from Glaucium flavum, which revealed predicted and novel enzyme activities.ConclusionsThis study establishes an essential resource for the isolation and discovery of 1) functional homologues and 2) entirely novel catalysts within BIA metabolism. Functional analysis of G. flavum NMTs demonstrated the utility of this resource and underscored the importance of empirical determination of proposed enzymatic function. Publically accessible, fully annotated, BLAST-accessible transcriptomes were not previously available for most species included in this report, despite the rich repertoire of bioactive alkaloids found in these plants and their importance to traditional medicine. The results presented herein provide essential sequence information and inform experiment...

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Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants

et al. 2015

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“…16) The F values of THP and THB are reportedly low: 2.5-17.8% for THP following oral administration of various formulations of Corydalis decumbens rhizome extracts at doses containing ca. 12 mg/kg THP 17) and 25.6% for THB following oral administration of 50 mg/kg THB. 13) Br/P ratios of both THP and THB were greater than unity (approximately 2-4) at 30, 120, and 360 min after single and multiple oral administration of DA-9701.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Brain Distribution of Tetrahydropalmatine and Tetrahydroberberine after Oral Administration of DA-9701, a New Botanical Gastroprokinetic Agent, in Rats

Jung

Kwon

Jeong

et al. 2015

Biological & Pharmaceutical Bulletin

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DA-9701 produces strong gastroprokinetic effects at an effective dose of 0.3-3 mg/kg in rats and its safety profile is superior to conventional prokinetics, such as cisapride, mosapride, itopride, and domperidone. 1)HPLC identified chlorogenic acid and corydaline as the major constituents in DA-9701. 5) Chlorogenic acid and corydaline have been selected as marker compounds to ensure consistent concentrations among batches of Pharbitidis semen and Corydalis tuber, respectively, and are known to be the active ingredients in DA-9701. Recently, the pharmacokinetics of chlorogenic acid and corydaline after intravenous and oral administration of pure chlorogenic acid, corydaline, or DA-9701 to rats were reported by our laboratory.6) Linear pharmacokinetics of chlorogenic acid were observed following intravenous (1-4 mg/kg) and oral (1-8 mg/kg) administration of chlorogenic acid or DA-9701. The extent of absolute oral bioavailability (F) of chlorogenic acid was extremely low, 0.478-0.899%, possibly because of incomplete absorption, decomposition in the gastrointestinal (GI) tract, and/or presystemic metabolism. The pharmacokinetics of corydaline were non-linear upon intravenous and oral administration of corydaline (1.1-4.5 mg/kg), possibly because of saturation of corydaline metabolism at higher doses. However, linear pharmacokinetics of corydaline were observed following oral administration of DA-9701. Besides chlorogenic acid and corydaline, DA-9701 contains tetrahydropalmatine (THP), tetrahydroberberine (THB), caffeic acid, coptisine, palmatine, berberine, and dehydrocorydaline (reports from Dong-A Pharmaceutical Co., Ltd.). Among these constituents, we focused on THP and THB (Figs. 1A, B, respectively) because of their dopamine D 2 receptor antagonizing activity (the IC 50 values of THP and THB against GTPγS binding to dopamine D 2S receptor in human recombinant Chinese hamster ovary (CHO) cells are 1.32 µM (469 ng/ mL) and 0.622 µM (211 ng/mL), respectively, according to preliminary reports from Dong-A Pharmaceutical Co., Ltd.). Other major constituents in DA-9701 including corydaline, chlorogenic acid, berberine, and palmatine did not show any activity on dopamine D 2 receptor at concentration ranges of 0.1-10 µM for corydaline and 0.1-1 µM for the others according to the radioligand ([

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“…Partial pharmacological blockade of GABA A receptors rescues the memory phenotype of D 1 -CB 1 -KO mice when injected immediately or 1h after learning. The fast pharmacodynamic clearance of the GABA A antagonist Bicuculline in rodents (Wu et al, 2013), suggests that the counteracting effect of this drug should be disappeared few hours after treatment, placing the mutant mice in similar conditions as in controls.…”

Section: Discussionmentioning

confidence: 99%

Specific hippocampal interneurons shape consolidation of recognition memory

Cruz

Busquets-García

Zhao

et al. 2019

Preprint

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A complex array of different inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically impacts on memory processes is scantly known. We found that a small subclass of type-1 cannabinoid receptor (CB 1 )-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D 1 receptor signaling to GABAergic transmission.Mice lacking CB 1 in D 1 -positive cells (D 1 -CB 1 -KO) displayed impaired long-term, but not short-term, object recognition memory. Re-expression of CB 1 in hippocampal, but not striatal, D 1 -positive cells rescued this memory impairment.Learning induced a facilitation of in vivo hippocampal long-term potentiation (LTP), which was abolished in mutant mice. Chemogenetic and pharmacological experiments revealed that both CB 1 -mediated memory and associated LTP facilitation involves the local control of GABAergic inhibition in a D 1 -dependent manner.This study reveals that CB 1 -/D 1 -expressing interneurons shape hippocampal circuits to sustain recognition memory, thereby identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral and cognitive outcomes.

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Comparative pharmacokinetics and bioavailability of four alkaloids in different formulations from Corydalis decumbens

Cited by 24 publications

References 19 publications

Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants

Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants

Pharmacokinetics and Brain Distribution of Tetrahydropalmatine and Tetrahydroberberine after Oral Administration of DA-9701, a New Botanical Gastroprokinetic Agent, in Rats

Specific hippocampal interneurons shape consolidation of recognition memory

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